Human histone demethylase KDM6B can catalyse sequential oxidations

Jumonji domain‐containing demethylases (JmjC‐KDMs) catalyse demethylation of Nε ‐methylated lysines on histones and play important rolesin gene regulation. We report selectivity studies on KDM6B (JMJD3), a disease‐relevant JmjC‐KDM, using synthetic lysine analogues. The results unexpectedly reveal that KDM6B accepts multiple Nε ‐alkylated lysine analogues, forming alcohol, aldehyde and carboxylic acid products

Additional file 6 of Metabolomics detects clinically silent neuroinflammatory lesions earlier than neurofilament-light chain in a focal multiple sclerosis animal model

Additional file 6: Table S2 The top 2 CSF metabolites differentiating DTH and control animals at day 12. *As multiple ‘bins’ are attributable to glucose, only those with a VIP rank of < 10 are shown

Additional file 5 of Metabolomics detects clinically silent neuroinflammatory lesions earlier than neurofilament-light chain in a focal multiple sclerosis animal model

Additional file 5: Table S1 The top 2 serum metabolites differentiating DTH and control animals at day 12

Additional file 3 of Metabolomics detects clinically silent neuroinflammatory lesions earlier than neurofilament-light chain in a focal multiple sclerosis animal model

Additional file 3: Fig. S3 Correlation between CSF and serum NfL concentrations. (A) In all animals at all time points, (B) stratified by treatment groups at all time points, and (C) within DTH animals stratified by time points. DTH: delayed-type hypersensitivity; NfL: neurofilament-light chain; r: Pearson correlation coefficien

Additional file 1 of Metabolomics detects clinically silent neuroinflammatory lesions earlier than neurofilament-light chain in a focal multiple sclerosis animal model

Additional file 1: Fig. S1 Weight of all animals at the 3 experimental time points. No weight differences were observed between the treatment groups at each time point on two-way ANOVA. ANOVA: analysis of variance; DTH: delayed-type hypersensitivit

Additional file 4 of Metabolomics detects clinically silent neuroinflammatory lesions earlier than neurofilament-light chain in a focal multiple sclerosis animal model

Additional file 4: Fig. S4 Comparison of clean vs. blood-contaminated CSF NMR spectra. (A) 1D-NOESY-presat spectra (chemical shift shown: 0.60 ppm – 4.20 ppm) demonstrating clean CSF (in blue) and blood-contaminated CSF (in red). This revealed aberrant NMR resonances contributed by lipoproteins and macromolecules (e.g. albumin) in blood, resulting in a broad signal with an elevated baseline (boxed region, chemical shift shown: 0.70 ppm – 1.40 ppm). (B) Zoom-in view of this boxed region showed additional resonances arising from the mobile methyl (CH3) and methylene (CH2) groups within lipoproteins, as well as from the branched chain amino acids (i.e. isoleucine, leucine, and valine). NMR: nuclear magnetic resonance; NOESY: nuclear overhauser effect spectroscopy; ppm: parts per millio

Additional file 2 of Metabolomics detects clinically silent neuroinflammatory lesions earlier than neurofilament-light chain in a focal multiple sclerosis animal model

Additional file 2: Fig. S2 CSF and serum NfL concentrations in control and naïve animals. No differences in NfL concentrations were observed between the 2 groups in both (A) CSF and (B) serum on two-way ANOVA. ANOVA: analysis of variance; NfL: neurofilament-light chai